臺灣博碩士論文加值系統

以二位置有取代之4-末位氯烷基氧喹唑啉衍生物為起始物的烷化反應中同時得到N位置取代及O位置取代之產物，靜置一段時間後O取代之產物透過1,3-O→N重排反應轉換成N取代之產物，起始物第四位置上為接有離去基的氯烷基氧，在進行1,3-O→N重排反應時必然經由不同於Chapman rearrangement的反應機制，由於反應的中間物不易捕抓，便藉由理論計算的方式對反應機制進行探討。以密度泛函數法B3LYP/6-31G（d）對4-末位氯烷基氧喹唑啉、3-末位氯烷基喹唑酮及1,3-azaoxonium的結構進行探討，由NBO的計算結果與能障的比較，得知1,3-azaoxonium傾向於斷O-C鍵而形成N取代的烷化產物，並由中間物O-C與N-C鍵長與能量之曲線圖找出反應的過度狀態與能障，從能階圖得知該1,3-O→N重排反應為兩階段反應，第一階段起始物形成環化之1,3-azaoxonium，此階段為反應的速率決定步驟，第二階段由氯離子攻擊中間物環上電子密度低的位置而開環形成產物。使用更高級的基底函數進行單點能量計算，但可能受到溶劑效應的影響，並未得到更精確的結果。

The alkylation of 2-substituted 4-(-chloroalkoxy)quinazoline derivatives gave the N- and O-alkylation products. However the O-alkylation products were transferred to the N-alkylation products through 1,3 -O→N shift in less a day. The mechanism is different from Chapman rearrangement because the reactants have leaving groups. The intermediate of the 1,3-O→N shift is hard to be trapped, so computational chemistry was used to explore the mechanism of the 1,3 -O→N shift. The optimized structures of 2-substituted 4-(-chloroalkoxy) quinazoline, 3-(-chloroalkyl)quinazoline-4(3H)-one and 1,3- azaoxonium were obtained with B3LYP(d)/6-31G(d). The NBO calculation and energy barrier show that 1,3-azaoxonium intermediates prefer to break the O-C bond because of lower energy barrier. The transition states of the 1,3-O→N shift were also located. The 1,3-O→N shift was proceeded by an intramolecular two-step mechanism via five- and six-membered 1,3-azaoxonium intermediates. First, 4-(- chloroalkoxy)quinazoline became the cyclic 1,3-azaoxonium and then chloride ion attacked the carbon which has lower electron density. The cyclic step is the rate-determining step. The higher basis set 6-311G(d,p) did not give satisfied results. The reason might be the solvent effect.

第一章 緒論 1
第二章 理論計算與方法 6
2.1 理論計算化學 6
2.2 計算方法種類 7
2.2.1 分子力學法 (Molecular Mechanics) 7
2.2.2 半經驗法 (Semi-empirical) 8
2.2.3 全計算法 (Ab initio) 9
2.2.4 密度泛函數理論法 (Density Functional Theory) 10
2.3 基底函數 （Basis Set） 11
2.3.1 極化函數 （Polarization Function） 12
2.3.2 擴散函數 （Diffuse Function） 12
2.4、Gaussian 03 計算套裝軟體 13
2.4.1、幾何優選化（Geometry Optimization） 14
2.4.2、單點能量（Single Point Energy） 15
2.4.3、振動頻率（Frequency） 15
第三章 結果與討論 16
第四章 結論 46
第五章 參考資料 46

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